Genomewide CRISPR knockout screen identified PLAC8 as an essential factor for SADS-CoVs infection
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Tse, Longping V, et al. Genomewide Crispr Knockout Screen Identified Plac8 As an Essential Factor for Sads-covs Infection. 2022. https://doi.org/10.17615/qvw2-wm33APA
Tse, L., Meganck, R., Araba, K., Yount, B., Shaffer, K., Hou, Y., Munt, J., Adams, L., Wykoff, J., Morowitz, J., Dong, S., Magness, S., Marzluff, W., Gonzalez, L., Ehre, C., & Baric, R. (2022). Genomewide CRISPR knockout screen identified PLAC8 as an essential factor for SADS-CoVs infection. https://doi.org/10.17615/qvw2-wm33Chicago
Tse, Longping V., Rita M Meganck, Kenza C Araba, Boyd L Yount, Kendall M Shaffer, Yixuan J Hou, Jennifer E Munt et al. 2022. Genomewide Crispr Knockout Screen Identified Plac8 As an Essential Factor for Sads-Covs Infection. https://doi.org/10.17615/qvw2-wm33- Creator
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Tse, Longping V.
- Affiliation: Gillings School of Global Public Health, Department of Epidemiology
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Meganck, Rita M.
- Affiliation: Gillings School of Global Public Health, Department of Epidemiology
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Araba, Kenza C.
- Affiliation: School of Medicine, Marsico Lung Institute/UNC Cystic Fibrosis Center
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Yount, Boyd L.
- Affiliation: Gillings School of Global Public Health, Department of Epidemiology
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Shaffer, Kendall M.
- Affiliation: School of Medicine, Marsico Lung Institute/UNC Cystic Fibrosis Center
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Hou, Yixuan J.
- Affiliation: Gillings School of Global Public Health, Department of Epidemiology
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Munt, Jennifer E.
- Affiliation: Gillings School of Global Public Health, Department of Epidemiology
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Adams, Lily E.
- Affiliation: Gillings School of Global Public Health, Department of Epidemiology
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Wykoff, Jason A.
- Affiliation: School of Medicine, Marsico Lung Institute/UNC Cystic Fibrosis Center
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Morowitz, Jeremy M.
- Affiliation: Center for Gastrointestinal Biology and Disease
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Dong, Stephanie
- Affiliation: Gillings School of Global Public Health, Department of Epidemiology
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Magness, Scott T.
- Affiliation: Center for Gastrointestinal Biology and Disease
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Marzluff, William F.
- Affiliation: School of Medicine, Department of Biochemistry and Biophysics
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Gonzalez, Liara M.
- Other Affiliation: North Carolina State University
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Ehre, Camille
- Affiliation: School of Medicine, Marsico Lung Institute/UNC Cystic Fibrosis Center
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Baric, Ralph S.
- Affiliation: Gillings School of Global Public Health, Department of Epidemiology
- Abstract
- Zoonotic transmission of coronaviruses poses an ongoing threat to human populations. Endemic outbreaks of swine acute diarrhea syndrome coronavirus (SADS-CoV) have caused severe economic losses in the pig industry and have the potential to cause human outbreaks. Currently, there are no vaccines or specific antivirals against SADS-CoV, and our limited understanding of SADS-CoV host entry factors could hinder prompt responses to a potential human outbreak. Using a genomewide CRISPR knockout screen, we identified placenta-associated 8 protein (PLAC8) as an essential host factor for SADS-CoV infection. Knockout of PLAC8 abolished SADS-CoV infection, which was restored by complementing PLAC8 from multiple species, including human, rhesus macaques, mouse, pig, pangolin, and bat, suggesting a conserved infection pathway and susceptibility of SADS-CoV among mammals. Mechanistically, PLAC8 knockout does not affect viral entry; rather, knockout cells displayed a delay and reduction in viral subgenomic RNA expression. In a swine primary intestinal epithelial culture (IEC) infection model, differentiated cultures have high levels of PLAC8 expression and support SADS-CoV replication. In contrast, expanding IECs have low levels of PLAC8 expression and are resistant to SADS-CoV infection. PLAC8 expression patterns translate in vivo; the immunohistochemistry of swine ileal tissue revealed high levels of PLAC8 protein in neonatal compared to adult tissue, mirroring the known SADS-CoV pathogenesis in neonatal piglets. Overall, PLAC8 is an essential factor for SADS-CoV infection and may serve as a promising target for antiviral development for potential pandemic SADS-CoV.
- Date of publication
- 2022
- Keyword
- DOI
- Identifier
- Resource type
- Article
- Rights statement
- In Copyright
- License
- Attribution-NonCommercial-NoDerivs 4.0 International
- Journal title
- Proceedings of the National Academy of Sciences
- Journal volume
- 119
- Journal issue
- 18
- Page start
- e2118126119
- Language
- English
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